PD-1-mediated inhibition of T cell activation: Mechanisms and strategies for cancer combination immunotherapy
Rui Liu,
Hui-Fang Li,
Shu Li
Affiliations
Rui Liu
Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Frontier Science Center for Immunology and Metabolism, Wuhan, 430071, China; Medical Research Institute, Wuhan, 430071, China; Research Unit of Innate Immune and Inflammatory Diseases (2019RU063), Chinese Academy of Medical Sciences, Wuhan, 430071, China; Wuhan University, Wuhan, 430071, China
Hui-Fang Li
Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Frontier Science Center for Immunology and Metabolism, Wuhan, 430071, China; Medical Research Institute, Wuhan, 430071, China; Research Unit of Innate Immune and Inflammatory Diseases (2019RU063), Chinese Academy of Medical Sciences, Wuhan, 430071, China; Wuhan University, Wuhan, 430071, China
Shu Li
Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China; Frontier Science Center for Immunology and Metabolism, Wuhan, 430071, China; Medical Research Institute, Wuhan, 430071, China; Research Unit of Innate Immune and Inflammatory Diseases (2019RU063), Chinese Academy of Medical Sciences, Wuhan, 430071, China; Wuhan University, Wuhan, 430071, China; Corresponding author. Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
The programmed cell death 1 (PD-1) immune checkpoint of co-inhibitory signaling plays crucial roles in controlling the magnitude and duration of T cell activation to limit tissue damage and maintain self-tolerance. Cancer cells hijack the co-inhibitory pathway and escape immune surveillance by overexpressing the PD-1 ligand PD-L1. Immune checkpoint inhibitors, such as PD-1 blocking antibody have been approved for tumor immunotherapy. However, not all patients can benefit from PD-1 monotherapy. Combination immunotherapy based on PD-1 axis blockade substantially improves clinical anti-tumor efficacy. In this review, we briefly summarize the current progress on the mechanisms of PD-1-mediated inhibition of T cell activation and strategies for cancer combination immunotherapy.